Tiny microbes, enormous impacts: what matters in gut microbiome studies?

Many factors affect the microbiomes of humans, mice, and other mammals, but substantial challenges remain in determining which of these factors are of practical importance. Considering the relative effect sizes of both biological and technical covariates can help improve study design and the quality of biological conclusions. Care must be taken to avoid technical bias that can lead to incorrect biological conclusions. The presentation of quantitative effect sizes in addition to P values will improve our ability to perform meta-analysis and to evaluate potentially relevant biological effects. A better consideration of effect size and statistical power will lead to more robust biological conclusions in microbiome studies

The NEBLINE, April 2011

Contents: Feature: Supplemental Kits Make Learning Nutrition Fun Farm Views Horticulture Food & Fitness Home & Family Living Environmental Focus Urban Agriculture 4-H & Youth Community Focus Extension Calendar Nutrition Education Program Family and Community Education (FCE) Clubs and other extension news and event

Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota.

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases

The NEBLINE, April 2011

Contents: Feature: Supplemental Kits Make Learning Nutrition Fun Farm Views Horticulture Food & Fitness Home & Family Living Environmental Focus Urban Agriculture 4-H & Youth Community Focus Extension Calendar Nutrition Education Program Family and Community Education (FCE) Clubs and other extension news and event

Footnotes, June, July, August 2006, Vol. 31, no. 6-7-8

Monthly newsletter of the State Librar

‘Managing pieces of a personal puzzle’ — older people’s experiences of self-management falls prevention exercise guided by a digital program or a booklet

Background: Exercise is effective in order to prevent falls in community-dwelling older people. Self-management programs have the potential to increase access and reduce costs related to exercise-based fall prevention. However, information regarding older people's views of participating in such programs is needed to support implementation. The aim of this study was to explore older people's experiences of a self-management fall prevention exercise routine guided either by a digital program (web-based or mobile) or a paper booklet. Methods: This qualitative study was part of a feasibility study exploring two completely self-managed exercise interventions in which the participants tailored their own program, guided either by a digital program or a paper booklet. Individual face-to-face semi-structured interviews were conducted with a purposeful sample of 28 participants (18 women), mean age 76yrs. Qualitative content analysis was used to analyse the data. Results: Self-managing and self-tailoring these exercise programs was experienced as Managing pieces of a personal puzzle'. To independently being able to create a program and manage exercise was described in the categories Finding my own level' and Programming it into my life'. The participants experienced the flexibility and independence provided by completely self-managed exercise as positive and constructive although it required discipline. Furthermore, different needs and preferences when managing their exercise were described, as well as varying sources of motivation for doing the exercise, as highlighted in the category Defining my source of motivation'. The category Evolving my acquired knowledge' captures the participants' views of building their competence and strategies for maintenance of the exercise. It describes a combined process of learning the program and developing reflection, which was more clearly articulated by participants using the digital program. Conclusions: This study provides new knowledge regarding experiences, preferences and motivations of older people to engage in home-based self-managed fall prevention exercise. They expressed both a capability and willingness to independently manage their exercise. A digital program seems to have strengthened the feeling of support while creating their own exercise program and tailoring it to their preferences and circumstances, which might therefore create better opportunities for adoption and adherence in the long term

CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders.

β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1-42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2-4 years). There was an overall reduction in Aβ42 from a mean concentration of 211-195 pg ml(-1) after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques

Laparoscopic-assisted percutaneous endoscopic gastrostomy: Insertion of a skin-level device using a tear-away sheath

Background: This study describes our experience with the placement of a skin-level gastrostomy device (MIC-KEY) in a single procedure. Methods: We identified infants, children and young adults who underwent laparoscopicassisted percutaneous endoscopic gastrostomy (LAPEG) tube insertion between October 2009 and June 2013. The steps of this procedure include upper endoscopy, single-port laparoscopy, gastropexy via percutaneous T-fasteners and placement of a skin-level gastrostomy device (MIC-KEY) using a push technique with a tearaway sheath. Results: We included 92 patients in our study. Mean age was 3.7 years (range 3 wk- 5 yr), and mean weight was 11.2 (range 2.8-54) kg. Median procedural time was 20 (range 12-76) minutes. Total median duration for the most recent 25 procedures was lower than that of the first 25 (62 v. 79 min, p = 0.004). There were no intraoperative complications or conversions to open surgery. Postoperative complications were observed in 6 (6.5%) patients. Three retained T-fasteners were assessed endoscopically (n = 1) or removed via local excision (n = 2). Two patients experienced early dislodged feeding tubes that were replaced via interventional radiology (n = 1) or repeat LAPEG (n = 1). There was also 1 intra-abdominal fluid collection that was drained percutaneously but ultimately required a laparotomy and washout. There were no major complications in the most recent 50 procedures. Conclusion: Our results suggest that LAPEG is a safe, minimally invasive procedure for infants, children and young adults. This approach allows for immediate use of a skin-level gastrostomy device without the need for postoperative tube exchanges

Overexpression of the protein kinase CK2 increases the survival and resistance to chemotherapy of acute myeloid leukemia cells

Background: The critical role of protein kinase CK2 in the regulation of cellular apoptosis suggests its may be involvement in tumor cell resistance to both conventional and unconventional therapies. Aim of the study: To study the role of CK2 in acute myeloid leukemia (AML) cell survival and response to chemotherapeutic agents. Methods: Apoptotic pathways were evaluated by AnnexinV/Propidium Iodide staining, Western Blot analysis of Caspase3 and Parp cleavage and Real Time PCR of antiapoptotic gene expression. Results: CK2 α catalytic subunit expression level and activity were increased in AML cells as compared to normal CD34+ hematopoietic cells. CK2 inactivation with the synthetic chemical inhibitors K27, CX-4945 or RNA interference induced AML cell apoptosis of p53 wild-type but not of p53-null cells, suggesting that the apoptosis triggered by CK2 inhibition needs the presence of functional p53. Inhibition of CK2 activity with K27 or CX-4945 was associated to an increased sensitivity of the cytotoxic effects of doxorubicin and daunorubicin. Cells were also nucleofected with siRNA oligos directed against CK2 α catalytic, β regulatory or both subunits. Interestingly RNA interference of CK2 β  reduced cell viability and enhanced apoptosis induced by daunorubicin, indicating a prominent role of this subunit in the resistance to chemotherapy. Based on our in-vitro results we have then examined the expression level of CK2 α and β in 32 newly diagnosed AML patients (excluding acute promyelocitic leukemia) from 2008 to 2011. Preliminary data shows a higher expression of the CK2 α subunit in the two AML subgroups with the highest risk based on cytogenetic characteristics. These laters nowadays represent the strongest prognostic factor predicting chemoresistance. Interestingly we did not find a correlation with expression of the regulatory subunit CK2 β. Conclusions: These data highlight the relevance of CK2 in AML cell survival for the influence of this kinase on the activation of anti-apoptotic pathways implicated in AML cell resistance to chemotherapy. A study to establish wether the CK2 expression at diagnosis represents an independent prognostic factor in the progression free survival and overall survival for these patients is needed